2090P - Management of trastuzumab deruxtecan-related nausea and vomiting in real-world practice

Background

Nausea and vomiting (N&V) are common side effects of Trastuzumab Deruxtecan (T-DXd), but guidelines for optimal management were not initially available. This retrospective study aimed to evaluate the efficacy of two different antiemetic regimens in patients (pts) receiving T-DXd.

Methods

We included 53 pts who received T-DXd at San Raffaele Hospital, Milan, with reliable information on antiemetic prophylaxis type and N&V severity (CTCAE 5.0 classification). Two groups were defined: pts treated with 5-HT3 receptor antagonists (RA) +/- dexamethasone (DEX) (5-HT3 group), and pts treated with a fixed oral combination of NK1RA (netupitant) and palonosetron +/- DEX (NK1 group). To be noted, that pts considered at higher risk of N&V by physician judgement were preferentially offered the NK1RA-containing regimen according to internal recommendations. Only N&V during cycles 1 (C1) and 2 (C2) were considered. Comparisons of N&V by antiemetic prophylaxis group were assessed by chi-square test.

Results

At C1, 15 (28.3%) and 38 (71.7%) pts were treated with and without NK1RA, respectively. Overall, 58.5% of pts reported nausea of any grade at C1, with no differences between the 5-HT3 and NK1 groups (57.9% vs 60%; p=0.832). A minimal numerical trend for lower grade of nausea in the NK1 (33.3% G1; 26.7% G2) compared to the 5-HT3 (23.7% G1; 31.6% G2; 2.6% G3) group was observed. Overall, 15.1% of pts reported vomiting of any grade during C1, with a borderline significant difference between the 5-HT3 (21%, all G1) and NK1 (0%) groups (p= 0.054). Among the 22 pts in the 5-HT3 group with nausea at C1, 15 (68.2%) immediately escalated to the NK1 regimen at C2. Among these, nausea decreased from 100% any grade (26.6% G1, 66.7% G2, 6.7% G3) at C1 to 53.3% any grade (13.3% G1, 40.0% G2) at C2 (p= 0.022), and vomiting decreased from 46.7% at C1 to 13.3% at C2 (all G1) (p=0.046).

Conclusions

The NK1RA-based regimen demonstrated a meaningful improvement in vomiting control at C1, and when promptly introduced as rescue at C2, significantly improved both nausea and vomiting. The biased preferential selection of NK1RA regimen for higher-risk pts may have dampened the differences in nausea control at C1. These results support the current 2023 NCCN antiemetic guidelines for T-DXd.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

L. Licata: Financial Interests, Personal, Advisory Board: Lilly, Exact Sciences, AstraZeneca, Italfarmaco, Daiichi Sankyo ; Financial Interests, Personal, Other, Consulting: Helsinn; Financial Interests, Personal, Invited Speaker: Eisai, Gilead, Exact Sciences. L. Sica: Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Novartis. G. Viale: Financial Interests, Personal, Advisory Board: Gilead; Financial Interests, Personal, Invited Speaker: Novartis, Lilly. G. Bianchini: Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo, Lilly, Novartis, Pfizer, Roche, Amgen, MSD, Chugai, Eisai, Gilead, Seagen, Exact Science, Roche, MSD, Gilead; Financial Interests, Personal, Other, Consultancy: AstraZeneca, Daiichi Sankyo, Roche, MSD, Gilead, Sanofi; Financial Interests, Personal, Invited Speaker: Lilly, Roche, AstraZeneca, Daiichi Sankyo, MSD, Chugai, Eisai, Gilead, Seagen, Neopharm Israel; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Roche, Pfizer, MSD, Chugai, Novartis, Gilead, Daiichi Sankyo; Financial Interests, Personal and Institutional, Steering Committee Member: Roche, Novartis, Lilly, AstraZeneca; Financial Interests, Institutional, Local PI: Gilead, Pfizer, Daiichi Sankyo, Lilly, MSD, Novartis; Non-Financial Interests, Leadership Role, Head of Translational Research: Fondazione Michelangelo. All other authors have declared no conflicts of interest.